RESUMEN
Monitoring chronic diseases, particularly kidney disorders, in people living with HIV (PLWH) is of paramount importance. Here, a systematic search was conducted across electronic search engine and databases like PubMed, Scopus, and Google Scholar, from date of inception until December 2023, to identify pertinent studies reporting on any association between inflammation and kidney function in PLWH. Only six clinical studies in peer-reviewed journals met the inclusion criteria, involving 1467 participants aged 37 to 51, with approximately 17% being females. The report emphasizes the potential impact of highly active antiretroviral therapy (HAART) on kidney function in PLWH, highlighting the significance of monitoring inflammation markers as indicators of kidney function, even when HAART is effective. Acknowledging study limitations, particularly the scarcity of relevant research, the findings highlight a need for more research to inform on clinical guidance to optimize HIV management, particularly regarding kidney health and HAART regimens. Although very limited studies were evaluated, the study lays an important foundation for future research to uncover the complex relationship between HAART, inflammation markers, and kidney health in PLWH.
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Terapia Antirretroviral Altamente Activa , Biomarcadores , Infecciones por VIH , Inflamación , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Biomarcadores/sangre , Femenino , Adulto , Masculino , Persona de Mediana Edad , Enfermedades Renales , Fármacos Anti-VIH/uso terapéutico , Riñón/fisiopatologíaRESUMEN
Background: Clinical studies have indicated a comorbidity between sepsis and kidney diseases. Individuals with specific mutations that predispose them to kidney conditions are also at an elevated risk for developing sepsis, and vice versa. This suggests a potential shared genetic etiology that has not been fully elucidated. Methods: Summary statistics data on exposure and outcomes were obtained from genome-wide association meta-analysis studies. We utilized these data to assess genetic correlations, employing a pleiotropy analysis method under the composite null hypothesis to identify pleiotropic loci. After mapping the loci to their corresponding genes, we conducted pathway analysis using Generalized Gene-Set Analysis of GWAS Data (MAGMA). Additionally, we utilized MAGMA gene-test and eQTL information (whole blood tissue) for further determination of gene involvement. Further investigation involved stratified LD score regression, using diverse immune cell data, to study the enrichment of SNP heritability in kidney-related diseases and sepsis. Furthermore, we employed Mendelian Randomization (MR) analysis to investigate the causality between kidney diseases and sepsis. Results: In our genetic correlation analysis, we identified significant correlations among BUN, creatinine, UACR, serum urate, kidney stones, and sepsis. The PLACO analysis method identified 24 pleiotropic loci, pinpointing a total of 28 nearby genes. MAGMA gene-set enrichment analysis revealed a total of 50 pathways, and tissue-specific analysis indicated significant enrichment of five pairs of pleiotropic results in kidney tissue. MAGMA gene test and eQTL information (whole blood tissue) identified 33 and 76 pleiotropic genes, respectively. Notably, genes PPP2R3A for BUN, VAMP8 for UACR, DOCK7 for creatinine, and HIBADH for kidney stones were identified as shared risk genes by all three methods. In a series of immune cell-type-specific enrichment analyses of pleiotropy, we identified a total of 37 immune cells. However, MR analysis did not reveal any causal relationships among them. Conclusions: This study lays the groundwork for shared etiological factors between kidney and sepsis. The confirmed pleiotropic loci, shared pathogenic genes, and enriched pathways and immune cells have enhanced our understanding of the multifaceted relationships among these diseases. This provides insights for early disease intervention and effective treatment, paving the way for further research in this field.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Enfermedades Renales , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Sepsis , Humanos , Sepsis/genética , Sepsis/epidemiología , Enfermedades Renales/genética , Pleiotropía GenéticaRESUMEN
OBJECTIVES: Uncoupling protein 2 (UCP2) was involved in the pathogenesis and development of kidney diseases. Many signaling pathways and factors regulate the expression of UCP2. We aimed to investigate the precise role of UCP2 and its signaling pathways in kidney diseases. METHODS: We summarized the available evidence to yield a more detailed conclusion of the signal transduction pathways of UCP2 and its role in the development and progression of kidney diseases. RESULTS: UCP2 could interact with 14.3.3 family proteins, mitochondrial phospholipase iPLA2γ, NMDAR, glucokinase, PPARγ2. There existed a signaling pathway between UCP2 and NMDAR, PPARγ. UCP2 can inhibit the ROS production, inflammatory response, and apoptosis, which may protect against renal injury, particularly AKI. Meanwhile UCP2 can decrease ATP production and inhibit the secretion of insulin, which may alleviate chronic renal damages, such as diabetic nephropathy and kidney fibrosis. CONCLUSIONS: Homeostasis of UCP2 is helpful for kidney health. UCP2 may play different roles in different kinds of renal injury.
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Transducción de Señal , Proteína Desacopladora 2 , Proteína Desacopladora 2/metabolismo , Humanos , Enfermedades Renales/metabolismo , Animales , Riñón/metabolismo , Riñón/patología , Apoptosis , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Objective: To investigate the clinicopathological features of renal leukocyte chemokine type 2 amyloidosis (ALECT2). Methods: The prevalence, clinical characteristics, renal histopathological features, and renal outcome of 15 patients with ALECT2 by kidney biopsy were collected in the Department of Kidney Pathology, Shanxi Medical University Second Hospital, Taiyuan, China from January 1993 to December 2023. Immunohistochemistry and mass spectrometry for amyloid proteins were carried out. Results: Fifteen patients with ALECT2 were included in the study, representing 12.93% (15/116) of the renal biopsy-proven amyloidosis cases. There were 5 males and 10 females. The median age at diagnosis was 61 years. All patients had various degrees of proteinuria; 7 patients had nephrotic syndrome; 3 patients had renal insufficiency; 7 patients had microscopic hematuria. Renal biopsy showed that strongly orangophilic amyloid proteins distributed mainly in the renal cortical interstitium, vascular walls, the glomerular mesangium and/or glomerular basement membrane. Eight cases were diagnosed with ALECT2 alone and 7 cases combined with other renal diseases, including 4 cases with membranous nephropathy, 2 cases with IgA nephropathy, and 1 case with subacute tubular interstitial nephropathy. ALECT2 patients with concurrent renal disease showed a higher proteinuria level than those without (3.48 g/24 h versus 4.58 g/24 h). All patients were corroborated by immunohistochemistry to exhibit the specific location of LECT2 in the amyloid fibrils. Mass spectrometry analysis revealed LECT2 polypeptide in 9 patients. Except two patients with worsening renal function, the others showed stable renal function during the mean follow-up period of 12.5 months. Conclusions: ALECT2 is the second common type of renal amyloidosis in our center. The majority of ALECT2 patients show concurrent renal diseases, with a high rate of membranous nephropathy. Amyloid deposits distribute mainly in the cortical interstitium of the kidney, the glomerular mesangium and vascular walls. Mass spectrometry is the most sensitive and specific method for detecting LECT2 amyloidosis.
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Amiloidosis , Enfermedades Renales , Riñón , Síndrome Nefrótico , Humanos , Masculino , Amiloidosis/metabolismo , Amiloidosis/patología , Amiloidosis/diagnóstico , Femenino , Persona de Mediana Edad , Síndrome Nefrótico/metabolismo , Síndrome Nefrótico/patología , Riñón/patología , Enfermedades Renales/patología , Enfermedades Renales/metabolismo , Proteinuria , Biopsia , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/metabolismo , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/metabolismo , Anciano , Hematuria/etiología , Insuficiencia Renal/metabolismoRESUMEN
Intravascular hemolysis is a central feature of congenital and acquired hemolytic anemias, complement disorders, infectious diseases, and toxemias. Massive and/or chronic hemolysis is followed by the induction of inflammation, very often with severe damage of organs, which enhances the morbidity and mortality of hemolytic diseases. Galectin-3 (Gal-3) is a ß-galactoside-binding lectin that modulates the functions of many immune cells, thus affecting inflammatory processes. Gal-3 is also one of the main regulators of fibrosis. The role of Gal-3 in the development of different kidney and liver diseases and the potential of therapeutic Gal-3 inhibition have been demonstrated. Therefore, the objective of this review is to discuss the possible effects of Gal-3 on the process of kidney and liver damage induced by intravascular hemolysis, as well as to shed light on the potential therapeutic targeting of Gal-3 in intravascular hemolysis.
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Galectina 3 , Hemólisis , Humanos , Galectina 3/metabolismo , Animales , Hepatopatías/metabolismo , Hepatopatías/etiología , Hepatopatías/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/etiología , Enfermedades Renales/patología , Riñón/metabolismo , Riñón/patologíaRESUMEN
OBJECTIVE: To explore the clinical effect of warm acupuncture with large-quantity moxibustion on primary premature ejaculation (kidney deficiency and liver stagnation). METHODS: A total of 240 patients with primary premature ejaculation (kidney deficiency and liver stagnation) were randomly divided into a warm acupuncture group (80 cases, 5 cases dropped out), an acupuncture group (80 cases, 4 cases dropped out) and a western medication group (80 cases, 6 cases dropped out). In the warm acupuncture group, a large quantity of moxibustion was delivered after acupuncture at Baihui (GV 20), Qihai (CV 6), Guanyuan (CV 4) and Zhongji (CV 3), as well as bilateral Fengchi (GB 20), lateral line 3 of forehead (MS 4), neishengzhiqi (TF2), Ganshu (BL 18), Shenshu (BL 23), and etc. One treatment with warm acupuncture took 40 min, once daily; five treatments were given per week and 4 weeks of treatment was required. In the acupuncture group, moxibustion was not delivered, and the rest operation of acupuncture was same as the warm acupuncture group. In the western medication group, dapoxetine hydrochloride tablets were administered orally, 30 mg each time, taken with warm water 1 h to 3 h before sexual intercourse. Medication was administered at most once within 24 h, twice per week, and 6 times within 4 weeks. Before and after treatment, the score of TCM symptoms, the score of premature ejaculation diagnostic tool (PEDT), intravaginal ejaculation latency time (IELT) and the serum sex hormone content (testosterone [T], luteinizing hormone [LH] and follicule stimulating hormone [FSH]) were observed and the clinical effect was evaluated in the three groups. RESULTS: After treatment, the scores for less duration of intercourse (<1 min), post-ejaculation fatigue, low spirit and decreased libido, and the total scores of TCM symptoms, as well as PEDT scores were reduced when compared with those before treatment in each group (P<0.01, P<0.05), and IELT was prolonged (P<0.01) in the three groups. The serum T content was increased when compared with that before treatment in the warm acupuncture group (P<0.05). After treatment, in comparison with the acupuncture group and the western medication group, the scores for post-ejaculation fatigue, soreness and weakness in the lumbar region and knee joints, decreased libido, insomnia, dream-disturbed sleep and frequent nocturnal enuresis, as well as the total score of TCM symptoms were lower (P<0.05, P<0.01) and the serum T content was increased (P<0.05) in the warm acupuncture group. When compared with the acupuncture group, PEDT scores were lower and IELT prolonged in the warm acupuncture group and the western medication group (P<0.05, P<0.01). The total effective rate was 82.7% (62/75) in the warm acupuncture group, higher than that of the acupuncture group (68.4%, 52/76) and the western medication group (64.9%, 48/74, P<0.05) respectively. CONCLUSION: Warm acupuncture with large-quantity moxibustion ameliorates the clinical symptoms and increases intravaginal ejaculation latency time and the levels of sex hormone in the patients with primary premature ejaculation (kidney deficiency and liver stagnation).
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Terapia por Acupuntura , Moxibustión , Eyaculación Prematura , Humanos , Masculino , Adulto , Eyaculación Prematura/terapia , Eyaculación Prematura/fisiopatología , Adulto Joven , Persona de Mediana Edad , Riñón/fisiopatología , Resultado del Tratamiento , Enfermedades Renales/terapia , Enfermedades Renales/fisiopatología , Puntos de Acupuntura , Hepatopatías/terapia , Hígado/fisiopatología , Hígado/metabolismoRESUMEN
Copper is a trace element essential for numerous biological activities, whereas the mitochondria serve as both major sites of intracellular copper utilization and copper reservoir. Here, we investigated the impact of mitochondrial copper overload on the tricarboxylic acid cycle, renal senescence and fibrosis. We found that copper ion levels are significantly elevated in the mitochondria in fibrotic kidney tissues, which are accompanied by reduced pyruvate dehydrogenase (PDH) activity, mitochondrial dysfunction, cellular senescence and renal fibrosis. Conversely, lowering mitochondrial copper levels effectively restore PDH enzyme activity, improve mitochondrial function, mitigate cellular senescence and renal fibrosis. Mechanically, we found that mitochondrial copper could bind directly to lipoylated dihydrolipoamide acetyltransferase (DLAT), the E2 component of the PDH complex, thereby changing the interaction between the subunits of lipoylated DLAT, inducing lipoylated DLAT protein dimerization, and ultimately inhibiting PDH enzyme activity. Collectively, our study indicates that mitochondrial copper overload could inhibit PDH activity, subsequently leading to mitochondrial dysfunction, cellular senescence and renal fibrosis. Reducing mitochondrial copper overload might therefore serve as a strategy to rescue renal fibrosis.
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Senescencia Celular , Cobre , Fibrosis , Riñón , Mitocondrias , Complejo Piruvato Deshidrogenasa , Cobre/metabolismo , Mitocondrias/metabolismo , Fibrosis/metabolismo , Animales , Complejo Piruvato Deshidrogenasa/metabolismo , Riñón/metabolismo , Riñón/patología , Acetiltransferasa de Residuos Dihidrolipoil-Lisina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Humanos , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Ciclo del Ácido CítricoRESUMEN
OBJECTIVE: This paper presents an analysis of the pregnancy trajectory and therapeutic regimen documentation of a primigravida with APSN. It aims at communicating the therapeutic approach and preventive measures for APSN in pregnancy. CASE PRESENTATION: This paper reports the trajectory and therapeutic regimen documentation of a primigravida with APSN. The APSN was discovered in a primigravida woman aged 26 years at 11 weeks of gestation. The initial therapy regimen consists of daily administration of prednisone 10 mg, hydroxychloroquine 200 mg, dapparin 5000 IU, and aspirin 50 mg. At a gestational age of 20 + 3 weeks, the dosage of dapparin was modified to 5000 IU/other day, along with a significant rise in urinary protein level seen at 30 + 3 weeks of gestational age. The initial dosage of dapanin sodium was renewed. The patient delivered at 38 + 3 weeks of gestation without other complications. CONCLUSION: It is imperative to acknowledge that altering the dosage and administration of medication should not be done haphazardly during pregnancy.
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Síndrome Antifosfolípido , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Adulto , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/complicaciones , Complicaciones del Embarazo/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Aspirina/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Prednisona/uso terapéuticoAsunto(s)
Absceso , Candida albicans , Candidiasis , Stents , Humanos , Stents/efectos adversos , Candidiasis/microbiología , Candidiasis/diagnóstico , Candida albicans/aislamiento & purificación , Absceso/microbiología , Absceso/diagnóstico por imagen , Masculino , Enfermedades Renales/microbiología , Tomografía Computarizada por Rayos X , Persona de Mediana EdadRESUMEN
We determined the epigenetic mechanisms regulating mean arterial pressure (MAP) and renal dysfunction in guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene-targeted mice. The Npr1 (encoding NPRA) gene-targeted mice were treated with class 1 specific histone deacetylase inhibitor (HDACi) mocetinostat (MGCD) to determine the epigenetic changes in a sex-specific manner. Adult male and female Npr1 haplotype (1-copy; Npr1+/-), wild-type (2-copy; Npr1+/+), and gene-duplicated heterozygous (3-copy; Npr1++/+) mice were intraperitoneally injected with MGCD (2 mg/kg) for 14 days. BP, renal function, histopathology, and epigenetic changes were measured. One-copy male mice showed significantly increased MAP, renal dysfunction, and fibrosis than 2-copy and 3-copy mice. Furthermore, HDAC1/2, collagen1alpha-2 (Col1α-2), and alpha smooth muscle actin (α-SMA) were significantly increased in 1-copy mice compared with 2-copy controls. The expression of antifibrotic microRNA-133a was attenuated in 1-copy mice but to a greater extent in males than females. NF-κB was localized at significantly lower levels in cytoplasm than in the nucleus with stronger DNA binding activity in 1-copy mice. MGCD significantly lowered BP, improved creatinine clearance, and repaired renal histopathology. The inhibition of class I HDACs led to a sex-dependent distinctive stimulation of acetylated positive histone marks and inhibition of methylated repressive histone marks in Npr1 1-copy mice; however, it epigenetically lowered MAP, repaired renal fibrosis, and proteinuria and suppressed NF-kB differentially in males versus females. Our results suggest a role for epigenetic targets affecting hypertension and renal dysfunction in a sex-specific manner.
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Presión Sanguínea , Epigénesis Genética , Receptores del Factor Natriurético Atrial , Animales , Femenino , Masculino , Receptores del Factor Natriurético Atrial/genética , Receptores del Factor Natriurético Atrial/metabolismo , Ratones , Presión Sanguínea/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Inhibidores de Histona Desacetilasas/farmacología , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Enfermedades Renales/patologíaRESUMEN
MicroRNAs (miRNAs) are 18-25 nucleotides long, single-stranded, non-coding RNA molecules that regulate gene expression. They play a crucial role in maintaining normal cellular functions and homeostasis in organisms. Studies have shown that miR-124-3p is highly expressed in brain tissue and plays a significant role in nervous system development. It is also described as a tumor suppressor, regulating biological processes like cancer cell proliferation, apoptosis, migration, and invasion by controlling multiple downstream target genes. miR-124-3p has been found to be involved in the progression of various kidney diseases, including diabetic kidney disease, calcium oxalate kidney stones, acute kidney injury, lupus nephritis, and renal interstitial fibrosis. It mediates these processes through mechanisms like oxidative stress, inflammation, autophagy, and ferroptosis. To lay the foundation for future therapeutic strategies, this research group reviewed recent studies on the functional roles of miR-124-3p in renal diseases and the regulation of its downstream target genes. Additionally, the feasibility, limitations, and potential application of miR-124-3p as a diagnostic biomarker and therapeutic target were thoroughly investigated.
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Enfermedades Renales , MicroARNs , MicroARNs/metabolismo , MicroARNs/genética , Humanos , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/genética , Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , Animales , Estrés Oxidativo , Nefritis Lúpica/genética , Nefritis Lúpica/metabolismo , Cálculos Renales/genética , Cálculos Renales/metabolismoRESUMEN
BACKGROUND: The American Heart Association (AHA) has recently introduced the concept of Cardiovascular-Kidney-Metabolic (CKM) syndrome, which is the result of an increasing emphasis on the interplay of metabolic, renal and cardiovascular diseases (CVD). Furthermore, there is substantial evidence of a correlation between the triglyceride glucose-body mass index (TyG-BMI ) and CVD as an assessment of insulin resistance (IR). However, it remains unknown whether this correlation exists in population with CKM syndrome. METHODS: All data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS). The exposure was the participants' TyG-BMI at baseline, which was calculated using a combination of triglycerides (TG), fasting blood glucose (FBG) and body mass index (BMI). The primary outcome was CVD, which were determined by the use of a standardised questionnaire during follow-up. To examine the relationship between TyG-BMI and CVD incidence in population with CKM syndrome, both Cox regression analyses and restricted cubic spline (RCS) regression analyses were performed. RESULTS: A total of 7376 participants were included in the final analysis. Of these, 1139, 1515, 1839, and 2883 were in CKM syndrome stages 0, 1, 2, and 3, respectively, at baseline. The gender distribution was 52.62% female, and the mean age was 59.17 ± 9.28 (years). The results of the fully adjusted COX regression analyses indicated that there was a 6.5% increase in the risk of developing CVD for each 10-unit increase in TyG-BMI,95% confidence interval (CI):1.041-1.090. The RCS regression analyses demonstrated a positive linear association between TyG-BMI and the incidence of CVD in the CKM syndrome population (P for overall < 0.001, P for nonlinear = 0.355). CONCLUSIONS: This cohort study demonstrated a positive linear association between TyG-BMI index and increased CVD incidence in a population with CKM syndrome stage 0-3. This finding suggests that enhanced assessment of TyG-BMI index may provide a more convenient and effective tool for individuals at risk for CVD in CKM syndrome stage 0-3.
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Biomarcadores , Glucemia , Índice de Masa Corporal , Enfermedades Cardiovasculares , Síndrome Metabólico , Triglicéridos , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/sangre , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/sangre , Estudios Prospectivos , Medición de Riesgo , Triglicéridos/sangre , Incidencia , Anciano , China/epidemiología , Glucemia/metabolismo , Factores de Tiempo , Biomarcadores/sangre , Pronóstico , Enfermedades Renales/epidemiología , Enfermedades Renales/diagnóstico , Enfermedades Renales/sangre , Estudios Longitudinales , Factores de Riesgo de Enfermedad Cardiaca , Resistencia a la Insulina , Factores de RiesgoRESUMEN
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is one of the fundamental mechanisms of the body's defense, which responds to the abnormal presence of double-stranded DNA in the cytoplasm to establish an effective natural immune response. In addition to detecting microbial infections, the cGAS pathway may be triggered by any cytoplasmic DNA, which is absent from the normal cytoplasm, and only conditions such as senescence and mitochondrial stress can lead to its leakage and cause sterile inflammation. A growing body of research has shown that the cGAS-STING pathway is strongly associated with sterile inflammation. In this study, we reviewed the regulatory mechanisms and biological functions of the cGAS-STING pathway through its involvement in aseptic inflammation in liver disease, kidney disease, and cellular senescence.
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Senescencia Celular , Enfermedades Renales , Hepatopatías , Proteínas de la Membrana , Nucleotidiltransferasas , Transducción de Señal , Humanos , Nucleotidiltransferasas/metabolismo , Senescencia Celular/inmunología , Proteínas de la Membrana/metabolismo , Enfermedades Renales/inmunología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Animales , Hepatopatías/inmunología , Hepatopatías/metabolismoRESUMEN
Macrophage alternative activation is involved in kidney fibrosis. Previous researches have documented that the transcriptional regulators Yes-associated protein (Yap)/transcriptional coactivator with PDZ-binding motif (Taz) are linked to organ fibrosis. However, limited knowledge exists regarding the function and mechanisms of their downstream molecules in regulating macrophage activation and kidney fibrosis. In this paper, we observed that the Hippo pathway was suppressed in macrophages derived from fibrotic kidneys in mice. Knockout of Taz or Tead1 in macrophages inhibited the alternative activation of macrophages and reduced kidney fibrosis. Additionally, by using bone marrow-derived macrophages (BMDMs), we investigated that knockout of Taz or Tead1 in macrophages impeded both cell proliferation and migration. Moreover, deletion of Tead1 reduces p-Smad3 and Smad3 abundance in macrophages. And chromatin immunoprecipitation (ChIP) assays showed that Tead1 could directly bind to the promoter region of Smad3. Collectively, these results indicate that Tead1 knockout in macrophages could reduce TGFß1-induced phosphorylation Smad3 via transcriptional downregulation of Smad3, thus suppressing macrophage alternative activation and IRI-induced kidney fibrosis.
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Proteínas de Unión al ADN , Fibrosis , Activación de Macrófagos , Macrófagos , Ratones Noqueados , Proteína smad3 , Factores de Transcripción de Dominio TEA , Factores de Transcripción , Animales , Proteína smad3/metabolismo , Proteína smad3/genética , Ratones , Macrófagos/inmunología , Macrófagos/metabolismo , Activación de Macrófagos/genética , Activación de Macrófagos/inmunología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Riñón/patología , Riñón/metabolismo , Transducción de Señal , Regulación hacia Arriba , Enfermedades Renales/genética , Enfermedades Renales/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/inmunología , Vía de Señalización Hippo , Modelos Animales de Enfermedad , Factor de Crecimiento Transformador beta1/metabolismo , Ratones Endogámicos C57BL , Masculino , Fosforilación , Proliferación Celular , AciltransferasasRESUMEN
Renal fibrosis (RF) is one of the underlying pathological conditions leading to progressive loss of renal function and end-stage renal disease (ESRD). Over the years, various therapeutic approaches have been explored to combat RF and prevent ESRD. Despite significant advances in understanding the underlying molecular mechanism(s), effective therapeutic interventions for RF are limited. Current therapeutic strategies primarily target these underlying mechanisms to halt or reverse fibrotic progression. Inhibition of transforming growth factor-ß (TGF-ß) signaling, a pivotal mediator of RF has emerged as a central strategy to manage RF. Small molecules, peptides, and monoclonal antibodies that target TGF-ß receptors or downstream effectors have demonstrated potential in preclinical models. Modulating the renin-angiotensin system and targeting the endothelin system also provide established approaches for controlling fibrosis-related hemodynamic changes. Complementary to pharmacological strategies, lifestyle modifications, and dietary interventions contribute to holistic management. This comprehensive review aims to summarize the underlying mechanisms of RF and provide an overview of the therapeutic strategies and novel antifibrotic agents that hold promise in its treatment.
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Antifibróticos , Fibrosis , Humanos , Fibrosis/tratamiento farmacológico , Antifibróticos/uso terapéutico , Antifibróticos/farmacología , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/patología , Animales , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Various rare inherited disorders can be associated with kidney involvement, including glomerulopathies, tubulopathies, multiple cysts, congenital anomalies of the kidneys and urinary tract, urolithiasis, malignant and benign tumors. Genetic nephropathy should be always considered in children, adolescents and young patients with the kidneys or urinary tract disorders and/or patients with positive family anamnesis. Extrarenal manifestations can be a valuable clue for diagnosis of certain hereditary diseases, e.g. neurosensory deafness in Alport syndrome or photofobia in nephropathic cystinosis. Diagnosis of monogenic inherited diseases should be verified by genetic testing. Specific drugs are available for treatment of certain hereditary diseases involving kidney, e.g. Fabry disease, cystinosis, primary hyperoxaluria I type and atypical hemolytic uremic syndrome.
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Enfermedades Renales , Enfermedades Raras , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/genética , Enfermedades Renales/etiología , Pruebas Genéticas/métodos , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/genética , Enfermedades Genéticas Congénitas/complicacionesRESUMEN
INTRODUCTION: Herlyn-Werner-Wunderlich syndrome , a rare Müllerian ducts congenital disease, is characterized by a diphtheritic uterus, blind hemivagina, and ipsilateral renal agenesis. Diagnosis is at young age by ultrasound and magnetic resonance imaging, and the prognosis is good. Usually, complications evolve endometriosis and secondary pelvic inflammation. CASE REPORT: A 40-year-old female patient, Brazilian, white, primigravida, diagnosed at 30 years with a didelphic uterus on ultrasound, and 4 years later, with a left ovarian endometrioma, multiple ovarian cysts, and left renal agenesis on magnetic resonance imaging. Subsequently, due to dyspareunia and a feeling of swelling, the patient underwent transvaginal ultrasound with bowel preparation, and a hematocolpos was found and Herlyn-Werner-Wunderlich syndrome was suspected; 10 years after the diagnosis she had a planned pregnancy. She presented frequent contractions following the 15th week of pregnancy and fortunately there were no complications or premature labor. Labor was inducted at 40 weeks and 6 days without progress and a cesarean section was indicated and performed without complications. Herlyn-Werner-Wunderlich syndrome often goes unnoticed, leading to inadequate treatment. Individuals with Herlyn-Werner-Wunderlich syndrome commonly face fertility issues, such as high miscarriage rate (21-33%), and obstetric complications, such as spontaneous abortions (40% risk), intrauterine growth restriction, postpartum hemorrhage, increased fetal mortality, preterm delivery (21-29%), and elevated rates of cesarean sections. In addition, there is higher susceptibility of developing endometriosis, especially with hemivaginal obstruction, and pelvic adhesions. CONCLUSION: Early diagnosis enables timely treatment and, consequently, fewer complications. Still, when these factors are absent, vaginal birth may still be possible. The true prevalence and incidence of complications related to Herlyn-Werner-Wunderlich syndrome are still unknown.
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Endometriosis , Humanos , Femenino , Adulto , Endometriosis/complicaciones , Embarazo , Útero/anomalías , Útero/diagnóstico por imagen , Cesárea , Riñón/anomalías , Conductos Paramesonéfricos/anomalías , Anomalías Múltiples , Anomalías Congénitas/diagnóstico , Anomalías Congénitas/diagnóstico por imagen , Vagina/anomalías , Complicaciones del Embarazo , Enfermedades Renales/congénito , Enfermedades Renales/diagnósticoRESUMEN
The KDIGO Update 2024 was supplemented by new "Clinical Practice Points", which were derived from the current evidence but are not necessarily comprehensively proven by prospective controlled studies. The most significant change in the Update 2024 for Lupus nephritis concerns the recommendations for induction therapy for lupus nephritis classes III and IV. The basis is still high-dose glucocorticoid treatment and the use of hydroxychloroquine. The 2 new developments in the 2024 Update concerning ANCA-associated nephritis are based on the studies on the use of the C5a receptor inhibitor Avacopan and the increasing data on induction protocols with reduced glucocorticoid dosage. Due to the inconsistency and variability of the conditions under which blood pressure measurements are carried out in practice, an international consensus statement was issued which defines 4 steps to achieve sufficient validity of the measurement results. CKD-MBD Controversies Conference 2023: The update for CKD-MBD, which was discussed in the Controversies Conference 2023, is in progress and has not been released yet. However, there were no serious contradictions between the 2023 data and the 2017 guidelines - the risk assessment regarding calcium-containing phosphate binders may have been put into perspective.
Asunto(s)
Guías de Práctica Clínica como Asunto , Humanos , Nefritis Lúpica/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Enfermedades Renales/terapia , Hidroxicloroquina/uso terapéuticoRESUMEN
BACKGROUND: Despite accumulating evidence of an association between air pollution and renal disease, studies on the association between long-term exposure to air pollution and renal function are still contradictory. This study aimed to investigate this association in a large population with relatively low exposure and with improved estimation of renal function as well as renal injury biomarkers. METHODS: We performed a cross-sectional analysis in the middle-aged general population participating in the Swedish CardioPulmonary bioImaging Study (SCAPIS; n = 30 154). Individual 10-year exposure to total and locally emitted fine particulate matter (PM2.5), inhalable particulate matter (PM10), and nitrogen oxides (NOx) were modelled using high-resolution dispersion models. Linear regression models were used to estimate associations between exposures and estimated glomerular filtration rate (eGFR, combined creatinine and cystatin C) and serum levels of renal injury biomarkers (KIM-1, MCP-1, IL-6, IL-18, MMP-2, MMP-7, MMP-9, FGF-23, and uric acid), with consideration of potential confounders. RESULTS: Median long-term PM2.5 exposure was 6.2 µg/m3. Almost all participants had a normal renal function and median eGFR was 99.2 mL/min/1.73 m2. PM2.5 exposure was associated with 1.3% (95% CI 0.6, 2.0) higher eGFR per 2.03 µg/m3 (interquartile range, IQR). PM2.5 exposure was also associated with elevated serum matrix metalloproteinase 2 (MMP-2) concentration, with 7.2% (95% CI 1.9, 12.8) higher MMP-2 per 2.03 µg/m3. There was a tendency towards an association between PM10 and higher levels of uric acid, but no associations were found with the other biomarkers. Associations with other air pollutants were null or inconsistent. CONCLUSION: In this large general population sample at low exposure levels, we found a surprising association between PM2.5 exposure and a higher renal filtration. It seems unlikely that particle function would improve renal function. However, increased filtration is an early sign of renal injury and may be related to the relatively healthy population at comparatively low exposure levels. Furthermore, PM2.5 exposure was associated with higher serum concentrations of MMP-2, an early indicator of renal and cardiovascular pathology.